The latest study from the Jill Roberts Institute, "CX3CR1+ mononuclear phagocytes control immunity to intestinal fungi," was published on January 11 in Science. To read more, click here.  Dr. Gregory Sonnenberg wins inaugural award from the Society for Mucosal Immunology. To read more, click here.  The Kenneth Rainin Foundation awarded Dr. Iliyan Iliev and colleagues from Mount Sinai a $250,000 Synergy Award to examine the composition of the fungal community in babies born to mothers with inflammatory bowel disease. To read more, click here. Dr. Randy Longman received the Irma T. Hirschl Career Scientist Award and the New York Crohn’s Foundation Award.    

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Different tissue phagocytes sample apoptotic cells to direct distinct homeostasis programs.

TitleDifferent tissue phagocytes sample apoptotic cells to direct distinct homeostasis programs.
Publication TypeJournal Article
Year of Publication2016
AuthorsCummings, RJ, Barbet, G, Bongers, G, Hartmann, BM, Gettler, K, Muniz, L, Furtado, GC, Cho, J, Lira, SA, J Blander, M
Date Published2016 11 24
KeywordsAmino Acids, Animals, Antigens, CD, Apoptosis, CD4-Positive T-Lymphocytes, Cell Differentiation, Cell Movement, Dendritic Cells, Epithelial Cells, Female, Homeostasis, Inflammation, Inflammatory Bowel Diseases, Integrin alpha Chains, Intestinal Mucosa, Lipid Metabolism, Lymph Nodes, Lymphocyte Activation, Macrophages, Male, Mice, Phagocytes, T-Lymphocytes, Regulatory, Transcription, Genetic

Recognition and removal of apoptotic cells by professional phagocytes, including dendritic cells and macrophages, preserves immune self-tolerance and prevents chronic inflammation and autoimmune pathologies. The diverse array of phagocytes that reside within different tissues, combined with the necessarily prompt nature of apoptotic cell clearance, makes it difficult to study this process in situ. The full spectrum of functions executed by tissue-resident phagocytes in response to homeostatic apoptosis, therefore, remains unclear. Here we show that mouse apoptotic intestinal epithelial cells (IECs), which undergo continuous renewal to maintain optimal barrier and absorptive functions, are not merely extruded to maintain homeostatic cell numbers, but are also sampled by a single subset of dendritic cells and two macrophage subsets within a well-characterized network of phagocytes in the small intestinal lamina propria. Characterization of the transcriptome within each subset before and after in situ sampling of apoptotic IECs revealed gene expression signatures unique to each phagocyte, including macrophage-specific lipid metabolism and amino acid catabolism, and a dendritic-cell-specific program of regulatory CD4(+) T-cell activation. A common 'suppression of inflammation' signature was noted, although the specific genes and pathways involved varied amongst dendritic cells and macrophages, reflecting specialized functions. Apoptotic IECs were trafficked to mesenteric lymph nodes exclusively by the dendritic cell subset and served as critical determinants for the induction of tolerogenic regulatory CD4(+) T-cell differentiation. Several of the genes that were differentially expressed by phagocytes bearing apoptotic IECs overlapped with susceptibility genes for inflammatory bowel disease. Collectively, these findings provide new insights into the consequences of apoptotic cell sampling, advance our understanding of how homeostasis is maintained within the mucosa and set the stage for development of novel therapeutics to alleviate chronic inflammatory diseases such as inflammatory bowel disease.

Alternate JournalNature
PubMed ID27828940
Grant ListAI095245 / / National Institutes of Health / International
AI123284 / / National Institutes of Health / International
DK072201 / / National Institutes of Health / International
2T32A1007605-11 / / National Institutes of Health / International
5T32DK007792-12 / / National Institutes of Health / International
5P01DK072201-09 / / National Institutes of Health / International
5R01CA161373-04 / / National Institutes of Health / International